Regeneron Phase III Stumble Shows RSV Market Is No Child's Play

Failure of Regeneron's anti-RSV antibody suptavumab (REGN2222) comes at a tough time for the company, as some marketed products disappoint and a long-time alliance with Sanofi comes to an end.

Regeneron Pharmaceuticals Inc.'s suptavumab antibody has dropped out of a long list of pipeline contenders aimed at the untapped and potentially vast market for preventing damage from respiratory syncytial virus (RSV) in infants, following the failure of a Phase III study.

Regeneron announced Aug. 14 that the candidate (previously called REGN2222) failed the primary endpoint for preventing medically-attended RSV infections in the Phase III, double-blind, controlled NURSERY study, which tested two regimens – 30 mg/kg as a single dose and 30 mg/kg as two doses given eight weeks apart – against placebo in children aged six months or younger. In the study, "medically-attended" meant cases where hospitalization or medical care was needed.

Suptavumab was developed with the company's proprietary VelociSuitetechnologies.

Although the adverse events were balanced between the study arms and there were "signs of efficacy in a subgroup of patients," the company said in a statement about the results that it is discontinuing development and declined further comment. Full results will be presented at a medical meeting.

RSV causes severe lower respiratory illness in children. According to the US Centers for Disease Control and Prevention, the condition is associated with 57,527 hospitalizations and 2.1 million outpatient visits each year among children under the age of five.

For a May meeting on clinical trials of RSV vaccines in infants, the US FDA noted in briefing documents that RSV is responsible for more than 30 million episodes of acute lower respiratory infection each year in children under the age of five. (Also see "FDA Panel To Weigh Animal, Adult Human Data For Initiation Of RSV Vaccine Trials In Infants" - Pink Sheet, 15 May, 2017.) The agency also noted that while there is a persistent unmet need, about 60 RSV candidates are in development.

MedImmune LLC/AstraZeneca PLC have enjoyed a monopoly on the market with Synagis (palivizumab), approved by the FDA since 1998 for preventing serious lower respiratory disease caused by RSV in high-risk children only.

According to the Biomedtracker database,Novavax Inc.'s RSV 7 vaccine is the only other RSV prevention candidate in Phase III development – the Prepare study is examining the candidate for use in maternal immunization to protect infants. Data are due in the fourth quarter.

Novavax had a major setback in November 2016 with the failure of RSV 7 in preventing RSV-associated illnesses in a Phase III study of adults over the age of 60, sending the company's stock price down by more than 83%. (Also see "Novavax’s Phase III RSV Vaccine Failure Wipes Out Nearly $2bn In Value" - Scrip, 16 Sep, 2016.)

However, Novavax announced positive topline results on July 24 from the Phase II E205 immunogenicity and safety study of another vaccine candidate, RSV F, with and without aluminum phosphonate or Novavax's proprietary Matrix-M adjuvant in adults.

"The data strongly support the inclusion of adjuvanted formulations of the RSV F vaccine in future older adult trials," Novavax said in its latest release.

Other companies with candidates in Phase II, according to Biomedtracker, are AstraZeneca/AIMM Therapeutics BV(MEDI-8897), Ablynx NV/Vectura Group PLC (ALX-0171), Johnson & Johnson (JNJ-53718678 and JNJ-64041575), Gilead Sciences Inc (presatovir) and GlaxoSmithKline PLC (GSK3003891A).

Datamonitor Healthcare analysts project that "pipeline vaccines will drive rapid growth of the RSV prophylaxis market to $2.6bn in the 2024/25 season."

Regeneron Looks Ahead To Other Milestones

Expectations appear to have been low for the candidate. Regeneron's stock price closed almost 8% higher at $474.54 on Aug. 14. But the RSV failure nevertheless comes at a bad time.

The company has been struggling to get the PCSK9 inhibiting antibody Praluent (alirocumab), partnered with Sanofi, off the ground, but has faced a very challenging payer environment and competitor Amgen Inc. is in the lead in terms of outcomes data with the release of the FOURIER study for Repatha (evolocumab). (Also see "PCSK9 Sales Still Slow, But May Get Boost From Label, Guideline Changes" - Scrip, 4 Aug, 2017.) Regeneron and Sanofi reported only €42m ($50m) in Praluent sales for the second quarter.

Regeneron's age-related macular degeneration (AMD) drug Eylea (aflibercept) performed well with $919m in sales for the quarter, but will face tough new competition from Novartis AG's brolucizumab. (Also see "Novartis' Brolucizumab Shows Dose Advantage Over Eylea In nAMD Trials" - Scrip, 20 Jun, 2017.)

Regeneron's IL-4/IL-13 blocker Dupixent (dupilumab), newly approved in March for moderate-to-severe atopic dermatitis, brought in sales of only $29m in the second quarter, disappointing analysts and raising concerns about whether the market potential for the indication has been overestimated. Dupixent also was developed with Sanofi.

The company recently announced that the antibody drug discovery partnership with Sanofi, which produced Dupixent and Praluent and the new rheumatology arthritis drug Kevzara (sarilumab), would be ending at the time of its expiration at the end of this year. (Also see "Regeneron And Sanofi Antibody Discovery Deal To End" - Scrip, 4 Aug, 2017.)

In its statement about the RSV news, Regeneron Chief Scientific Officer George Yancopoulos said that the company "has a robust pipeline across many serious diseases, and we look forward to important data readouts from other programs in the coming weeks and months."

The company highlighted many milestones for 2017 in its second-quarter earnings release (see table below).

Regeneron: Select 2017 Milestones
Product	Milestone(s)
Eylea	Submit sBLA to FDA for every 12-week dosing interval in neovascular age-related macular degeneration.
Dupixent	Submission for additional regulatory approvals in atopic dermatitis outside of the US. Regulatory agency decision on atopic dermatitis in the European Union. Report results from Phase III asthma program in adults and adolescents. Submit sBLA for asthma in adult/adolescent patients. Initiate Phase III studies with pediatric patients in atopic dermatitis.
Praluent	Complete ODYSSEY OUTCOMES study (with data expected in early 2018).
Suptavumab	Report results from Phase III study.
Kevzara	Submission for additional regulatory approvals and regulatory agency decisions on applications outside of the US.
REGN2810 (PD-1 antibody)	Initiate Phase III study in cervical cancer.
Fasinumab (NGF antibody)	Initiate Phase III study in chronic low back pain.
Nesvacumab/aflibercept (Ang2 antibody co-formulated with Eylea)	Report data from Phase II studies in diabetic macular edema (RUBY) and wet AMD (ONYX).
REGN2477 (Activin A antibody)	Initiate Phase II study in patients with Fibrodysplasia Ossificans Progressiva (FOP).
Source: Regeneron